홈MCP워크벤치Skills
홈워크벤치알림마이페이지
llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
  1. 홈
  2. /반응

Potassium Phosphate, Tribasic → tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate

HRID 1529259
노트
인쇄 미리보기

반응식

HRID 1529259 반응식
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:14]=[C:13]2[C:25]1[N:30]=[C:29]([N:31]2[CH2:36][CH2:35][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:33][CH2:32]2)[CH:28]=[N:27][CH:26]=1.[F:45][C:46]1[C:51]([O:52][CH3:53])=[CH:50][CH:49]=[CH:48][C:47]=1B(O)O>>[F:45][C:46]1[C:51]([O:52][CH3:53])=[CH:50][CH:49]=[CH:48][C:47]=1[C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:14]=[C:13]2[C:25]1[N:30]=[C:29]([N:31]2[CH2:32][CH2:33][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:41])([CH3:42])[CH3:43])[CH2:35][CH2:36]2)[CH:28]=[N:27][CH:26]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

4

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 67959723tert-butyl 1-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate2회

생성물 1

HCID 86709757tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate수율 54%

반응 조건

온도
150 °C

실험 절차

To a 5 mL conical microwave vial was added potassium phosphate (Aldrich, 129 mg, 0.61 mmol), PdCl2AmPhos (17.1 mg, 0.02 mmol), tert-butyl 1-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate (compound 1e, 135 mg, 0.24 mmol), and 2-fluoro-3-methoxyphenylboronic acid (Frontier Scientific, 45.3 mg, 0.27 mmol) which was sealed, evacuated and back-filled with N2 3×. Dioxane (2.0 mL) and water (0.4 mL) were added and the resulting mixture was heated at 150° C. for 30 min with microwave irradiation. After the reaction mixtures were filtered, the crude reaction mixture was concentrated under reduced pressure. The dark brown residue was dissolved with DMSO, filtered, and purified by HPLC (5% 0.1% TFA in water to 95% 0.1% TFA in ACN over 20 min) to give tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate (78.1 mg, 53.5%). MS (ESI, pos. ion) m/z: 603 (M+1). A mixture of 5N HCl in IPA (25.9 μL, 0.13 mmol), tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate (78.1 mg, 0.13 mmol), DCM (1.3 mL) and MeOH (1.3 mL) was heated at 80° C. for 30 min with stirring. The resulting reaction mixture was cooled to RT and concentrated to a yellow solid. The above solid was stirred with a 1:1 mixture of DCM:MeOH and applied to a pre-washed (10 mL MeOH) column of Si-propylsulfonic acid (Silicycle, Cat# R51230B). The compound was released with 30 mL of MeOH (with 2M NH3) to yield the title compound product as a yellow oil. MS (ESI, pos. ion) m/z: 419 (M+1).

후처리

  1. customwas sealed
  2. customevacuated
  3. additionback-filled with N2 3×
  4. additionDioxane (2.0 mL) and water (0.4 mL) were added
  5. customAfter the reaction mixtures
  6. filtrationwere filtered
  7. customthe crude reaction mixture
  8. concentrationwas concentrated under reduced pressure
  9. dissolutionThe dark brown residue was dissolved with DMSO
  10. filtrationfiltered
  11. custompurified by HPLC (5% 0.1% TFA in water to 95% 0.1% TFA in ACN over 20 min)

출처 및 근거

ORD 기록
ord-4f4687dd0e3c41f3be3b3dd288795dfc
출처 데이터셋
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09090593B2

반응 노트

불러오는 중…

이 페이지에서참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트